Identification of antidiabetic effect of iridoid glycosides and low molecular weight polyphenol fractions of Corni Fructus, a constituent of Hachimi-jio-gan, in streptozotocin-induced diabetic rats.

In our previous study, Corni Fructus (Cornus officinalis SIEB. et ZUCC.), a component crude drug of the Chinese prescription Hachimi-jio-gan, was reported to reduce glucotoxicities, up-regulate renal function, and consequently ameliorate glycation-associated renal damage as well as Hachimi-jio-gan. Based upon these facts, we prepared Corni Fructus fractions and evaluated which fraction contained the effective components against diabetes, using one iridoid glycoside and three polyphenol fractions, which were expected to possess stronger activities than Corni Fructus, administered orally at a dose of 20 mg/kg body weight/d for 10 d, respectively. As a result, iridoid glycosides and low molecular weight polyphenol fractions could reduce the pathogenesis of diabetic renal damage, each having different mechanisms, i.e., iridoid glycosides successfully decreased the hyperglycemic state and affected renal advanced glycation end-product (AGE) accumulation, such as N(epsilon)-(carboxyethyl)lysine and N(epsilon)-(carboxymethyl)lysine, while low molecular weight polyphenol fractions could reduce renal lipid peroxidation, the receptor for AGE, and inducible nitric oxide synthase. Overall, these data suggest that iridoid glycosides and low molecular weight polyphenols purified from Corni Fructus improve metabolic parameters associated with the development of diabetic renal damage. The main active components of these fractions are discussed.